This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This program project is a collaborative study with Dr. Lieberman (Harvard) to develop an effective microbicide based on small interfering RNA (siRNA) technology. We are also developing a model of herpesvirus transmission to determine if this can also be used to develop preventative microbicides. To date we have shown rhesus macaques are susceptible to HSV-1 and develop ulcerations, microvesicles, and inflammation in the vaginal epithelium and express HSV-1 genes for several weeks to months after infection. We have also tested siRNA technology against host nectin (the herpes binding receptor) and shown substantial downregulation occurs in the expression of nectin in vaginal epithelial cells when applied to macaques. We are currently repeating this experiment using carefully collected biopsies to determine the distribution of the downregulation of nectin to see if this can prevent against HSV-1 transmission.